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【结 构 式】 
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【分子编号】33105 【品名】ethyl 2,7-dichloro-4-(chloromethyl)-6-methyl-3-quinolinecarboxylate 【CA登记号】 |
【 分 子 式 】C14H12Cl3NO2 【 分 子 量 】332.61292 【元素组成】C 50.56% H 3.64% Cl 31.98% N 4.21% O 9.62% |
合成路线1
该中间体在本合成路线中的序号：(XI)Acylation of 3-chloro-4-methylaniline (VII) with chloroacetonitrile in the presence of BCl3 and Et2AlCl produced the chloroacetophenone (VIII). Subsequent condensation of (VIII) with ethylmalonyl chloride gave amide (IX), which was cyclized to the quinolinone (X) upon treatment with ethanolic NaOEt. Reaction of the quinolinone (X) with POCl3 afforded chloroquinoline (XI). The ester group of (XI) was then reduced to alcohol (XII) by means of diisobutylaluminum hydride. Condensation of (XII) with 4-methylpiperidine (XIII) gave adduct (IV), which was further coupled with pyridinone (VI) under Mitsunobu conditions to yield (Xv). Finally, intramolecular Heck reaction in the presence of palladium diacetate and triphenylphosphine provided the desired pentacyclic compound, which was isolated as the hydrochloride salt.
| 【1】 Coulomb, H.; Huchet, M.; Harnett, J.; Rolland, A.; Lanco, C.; Lavergne, O.; Demarquay, D.; Lesueur-Ginot, L.; Bigg, D.C.H.; BN 80927: A novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II. Bioorg Med Chem Lett 1999, 9, 17, 2599. |
| 【2】 Cazaux, J.-B.; Manginot, E.; Lavergne, O.; Le Breton, C.; Bigg, D. (SCRAS (Societé de Conseils de Recherches et d'Applications Scientifiques)); Optically pure camptothecin analogues, optically pure synthesis intermediate and method for preparing same. EP 1007527; FR 2768431; WO 9911646 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 33100 | (5R)-5-ethyl-5-hydroxy-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione | C11H13NO4 | 详情 | 详情 | |
| (VII) | 26794 | 3-Chloro-4-methylaniline; 4-Amino-2-chlorotoluene | 95-74-9 | C7H8ClN | 详情 | 详情 |
| (VIII) | 33102 | 1-(2-amino-4-chloro-5-methylphenyl)-2-chloro-1-ethanone | C9H9Cl2NO | 详情 | 详情 | |
| (IX) | 33013 | O-[tert-butyl(diphenyl)silyl]hydroxylamine; (aminooxy)(tert-butyl)diphenylsilane | C16H21NOSi | 详情 | 详情 | |
| (X) | 33104 | ethyl 7-chloro-4-(chloromethyl)-6-methyl-2-oxo-1,2-dihydro-3-quinolinecarboxylate | C14H13Cl2NO3 | 详情 | 详情 | |
| (XI) | 33105 | ethyl 2,7-dichloro-4-(chloromethyl)-6-methyl-3-quinolinecarboxylate | C14H12Cl3NO2 | 详情 | 详情 | |
| (XII) | 33106 | [2,7-dichloro-4-(chloromethyl)-6-methyl-3-quinolinyl]methanol | C12H10Cl3NO | 详情 | 详情 | |
| (XIII) | 10192 | 4-Methylpiperidine; gamma-Pipecoline | 626-58-4 | C6H13N | 详情 | 详情 |
| (XIV) | 33107 | [2,7-dichloro-6-methyl-4-[(4-methyl-1-piperidinyl)methyl]-3-quinolinyl]methanol | C18H22Cl2N2O | 详情 | 详情 | |
| (XV) | 33101 | (5R)-8-[(2-chloro-6,7-difluoro-3-quinolinyl)methyl]-5-ethyl-5-hydroxy-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione | C21H17ClF2N2O4 | 详情 | 详情 |